候选基因与月经初潮年龄相关，这些基因也与子宫内膜增生有关。

Candidate genes for age at menarche are associated with endometrial hyperplasia.

机构信息

Department of Medical Biological Disciplines, Belgorod State University, 308015 Belgorod, Russia.

出版信息

Gene. 2020 Oct 5;757:144933. doi: 10.1016/j.gene.2020.144933. Epub 2020 Jul 5.

DOI:10.1016/j.gene.2020.144933

PMID:32640302

Abstract

OBJECTIVES

To study associations candidate genes for age at menarche with a risk of endometrial hyperplasia (EH).

METHODS

52 candidate loci for age at menarche were analyzed for possible association with EH in a sample of 520 patients and 981 controls. Association of the polymorphisms was analyzed using the method of logistic regression. The gene-gene and gene-environment interactions were analyzed using MB-MDR. 21 polymorphisms, which were associated with EH, and 397 polymorphisms linked to them (r ≥ 0.8) were analyzed in silico for their functional significance.

RESULTS

21 out of the 52 studied polymorphisms had association with EH. Locus rs11031010 FSHB was individually associated with the disease according to the dominant (OR = 0.62, p = 0.001) and additive (OR = 0.67, p = 0.002) models. Haplotype GAA of loci rs555621-rs11031010-rs1782507 FSHB were associated with the EH (OR = 0.66, p = 0.007). Seventeen loci were associated with EH within 12 most significant models of intergenic interactions (p ≤ 0.001). Locus rs4374421 of the LHCGR gene appeared in the largest number of models (four models). Nine loci involved in 14 most significant models of interactions between SNP, induced abortions, and chronic endometritis were associated with EH. The polymorphisms of genes FTO (rs12324955) and FSHB (rs11031010) appeared in the largest number of the models (9 and 6, respectively). Among the 21 loci associated with EH, 16 manifested association also with either age at menarche (7 SNPs) or height and/or BMI (13 SNPs). The above 21 SNPs and 397 SNPs linked to them have non-synonymous, regulatory and eQTL significance for 25 genes, which play roles in the pathways related to development of the female reproductive organs and hormone-mediated signaling (FDR ≤ 0.05).

CONCLUSIONS

Candidate genes for age at menarche are associated with endometrial hyperplasia.

摘要

目的

研究与月经初潮年龄相关的候选基因与子宫内膜增生（EH）风险的关联。

方法

在 520 例患者和 981 例对照中分析了 52 个候选月经初潮年龄相关基因座，以研究其与 EH 的可能关联。使用逻辑回归分析多态性与疾病的关联。使用 MB-MDR 分析基因-基因和基因-环境相互作用。对与 EH 相关的 21 个多态性和与之相关的 397 个多态性（r≥0.8）进行了基于计算机的功能重要性分析。

结果

在所研究的 52 个多态性中，有 21 个与 EH 相关。根据显性（OR=0.62，p=0.001）和加性（OR=0.67，p=0.002）模型，FSHB 基因座 rs11031010 FSHB 单独与疾病相关。FSHB 基因座 rs555621-rs11031010-rs1782507 的 GAA 单倍型与 EH 相关（OR=0.66，p=0.007）。在 12 个最显著的基因间相互作用的模型中（p≤0.001），有 17 个与 EH 相关。LHCGR 基因的 rs4374421 基因座出现在 4 个模型中。在 14 个与 SNP、人工流产和慢性子宫内膜炎相互作用最显著的模型中，有 9 个基因座与 EH 相关。FTO（rs12324955）和 FSHB（rs11031010）基因座的多态性分别出现在 9 个和 6 个模型中。在与 EH 相关的 21 个基因座中，有 16 个也与月经初潮年龄（7 个 SNP）或身高和/或 BMI（13 个 SNP）相关。上述 21 个与 EH 相关的 SNP 和与之相关的 397 个 SNP 对 25 个基因具有非同义、调控和 eQTL 意义，这些基因在与女性生殖器官发育和激素介导的信号转导相关的途径中发挥作用（FDR≤0.05）。